慢性肾功能衰竭患者脂质过氧化物、超氧化物歧化酶及免疫功能状态的临床研究

目的：研究慢性肾功能衰竭（肾衰）患者氧自由基代谢和免疫功能状态的变化以及两者的关系。方法：测定８０例慢性肾衰患者和３０例正常人血清脂质过氧化物（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）、可溶性白细胞介素２受体（ＳＩＬ２Ｒ）和外周血Ｔ淋巴细胞亚群的水平并进行比较。结果：慢性肾衰患者血清ＬＰＯ、ＳＯＤ和ＳＩＬ２Ｒ水平较正常人明显升高（Ｐ均＜０．０１），外周血Ｔ淋巴细胞亚群ＣＤ＋３、ＣＤ＋４、ＣＤ＋８细胞及ＣＤ＋４／ＣＤ＋８比值则显著降低（Ｐ＜０．０５或Ｐ＜０．０１）。血清ＳＯＤ及ＳＩＬ２Ｒ水平与血肌酐（ＳＣｒ）呈显著正相关，与肾小球滤过率（ＧＦＲ）呈显著负相关；血清总ＳＯＤ、ＣｕＺｎＳＯＤ活性与ＳＩＬ２Ｒ水平呈显著正相关。结论：慢性肾衰患者存在氧自由基的蓄积，脂质过氧化反应的病理性亢进和超氧化物歧化酶代偿性增高及免疫功能异常的病理改变；血清ＳＯＤ、ＳＩＬ２Ｒ水平可作为肾功能损害的客观指标。     

Reduced angiotensin II induced vascular reactivity in chronic renal failure

Eight patients with chronic renal failure before the stage of dialysis (Group 1), 11 patients on regular dialysis treatment (Group 2) and 14 healthy control subjects (Group 3) were studied before, during and after angiotensin II (AII)-infusion. Blood pressure (BP), heart rate (HR), plasma levels of AII, aldosterone (Aldo), arginine vasopressin (AVP), noradrenaline (NA) and adrenaline (A), and serum concentrations of parathyroid hormone (PTH), calcium and magnesium were determined. AII induced vascular reactivity was reduced both in Group 1 and 2 compared with Group 3. Basal AII was the same in the three groups, and only in dialysis patients was AII induced vascular reactivity negatively correlated to basal AII. Aldo and NA were higher in Group 2 than in Group 3, and AVP was higher in both groups of patients compared with controls. HR declined during AII induced elevation of BP in the control subjects but not in the patients. Neither PTH, serum calcium nor serum magnesium was correlated to BP or vascular reactivity. It can be concluded that AII induced vascular reactivity is reduced both in patients with renal failure before dialysis and in patients on regular dialysis treatment. Basal blood levels of Aldo and NA are increased in dialysis patients and AVP is increased in both groups of patients, but neither these abnormalities nor blood levels of PTH, calcium or magnesium seem to be the background upon which the abnormal vascular reactivity develops.     

Interpretation of serum digoxin values in renal failure

We have studied three circumstances that have been reported to make interpretation of the serum digoxin concentration difficult in patients with renal failure: increased biotransformation; endogenous digitalis-like factors (DLF); and sudden, unexpected increases in serum digoxin values, even after the discontinuation of digoxin. Biotransformation, as estimated by the percent true digoxin in serum, was comparable in patients with renal failure who were dependent on dialysis and in control subjects (76% vs. 73%). Certain commercial immunoassays did not, or rarely, gave values for DLF of clinical significance (greater than 0.2 ng/ml digoxin equivalents) in patients with a wide range of renal dysfunction who were not receiving digoxin. With a sensitive method, values for DLF did not exceed 0.23 ng/ml in 22 dialysis patients dependent on dialysis, but were significantly increased in comparison with values in control subjects. The case histories of two patients with renal failure, acute illness, and sudden unexpected marked increases in serum digoxin concentrations are presented and possible explanations are discussed.     

Serial changes in cellular immunity of septic patients with multiple organ-system failure

Total lymphocyte count, lymphocyte cell-surface markers (OKT3, OKT4, OKT8, and B-1), serum complement factors (C3 and C4), immunoglobulins (IgG, IgA, and IgM), ceruloplasmin (Crl), and transferrin (Trf) were determined weekly for nine septic postoperative patients, all of whom had multiple organ-system failure. The peripheral blood total lymphocyte count, its subpopulation, T-cell subset, and proliferative responses of lymphocyte to phytohemagglutinin (PHA) and concanavalin A (Con A) decreased in all patients. OKT3 and B-1 decreased progressively in the four nonsurvivors compared with the five survivors. Although immunoglobulin levels were within the normal range in both groups, they tended to increase in survivors and decrease in nonsurvivors. Serial levels of C3, C4, Crl, and Trf increased in survivors but did not change in nonsurvivors. T-cell function and antibody-producing activity diminished progressively in nonsurvivors. These changes in cellular immunity may represent another manifestation of multiple organ-system failure during sepsis.     

Pathophysiology of acute renal failure at the cellular level

The influence of inflammation on post-ischemic acute renal failure (ARF) has only recently be appreciated. In this review we therefore discuss the cellular events occurring in ARF with special emphasis on the impact of inflammatory processes on the pathogenesis of ARF. Furthermore, the spectrum of injury leading to sublethal or lethal cell damage and the time course, occurrence and regulation of the two distinct forms of cell death, necrosis and apoptosis will be described extensively. Especially apoptosis and its regulation has been studied only marginally in the setting of ischemic ARF. This overview is mainly focused on tubular cell injury since tubular epithelial cells are the major victims of ischemia whereas cells inside the glomerular tuft show only little pathology. The models of tubular injury described in this paper are ranging from primary cultures of isolated human tubular epithelial cells to experimental ischemic renal failure in rats, and to clinical settings of human ischemic ARF. The cellular events highlighted in this review are the influence of the expression of cellular adhesion molecules on the pathophysiology of ARF, and the regulation and time course of apoptosis. Examples of these processes are being illustrated by figures exhibiting morphology and immunohistochemistry of cell proliferation and cell death regulatory proteins.     

急性肾衰竭患者血肾上腺髓质素的变化及临床意义

目的观察急性肾衰竭（ARF）患者血肾上腺髓质素（ADM）的变化,及与炎症因子（CRP、IL- 6、TNF-α）、肾功能（Scr）的相关性,探讨ADM在ARF炎症反应中的作用。方法选择山西医科大学第二医院确诊的单纯ARF患者76例作为病例组,健康人25人作为对照组;统一检测血ADM、CRF、IL-6、TNF-α及Scr水平。结果ARF患者血ADM、CRP、IL-6、TNF-α及Scr水平均高于正常对照组（P〈0．001）,且血ADM与炎症因子、肾功能水平呈显著正相关（P〈0．001）。结论单纯型ARF患者血ADM水平增高,与炎症介质、Scr之间呈显著正相关,因此ADM可能参与了ARF的炎症反应与肾功能的改善。     

胃肠癌患者术后抑郁反应对细胞免疫功能的影响

目的:探讨癌症患者手术后的抑郁情绪反应及淋巴细胞亚群和自然杀伤(NK)细胞变化规律。方法:对51例手术后3个月胃肠癌患者和22例健康对照者进行抑郁自评量表(SDS)评定并测定其CD3,CD4,CD8,NK细胞。结果:癌症组的SDS的评分明显高于正常对照组,29.4%有抑郁反应的,其中重度抑郁3.9%,中重度抑郁7.8%,轻中度抑郁17.6%。癌症Ⅲ,Ⅳ期的SDS评分(0.49±0.14)高于Ⅰ,Ⅱ期(0.40±0.10)。胃肠癌的CD3(63±11)低于正常对照组(68±6,t=1.982,P<0.05),CD4、CD4/CD8(26±9,1.9±1.0)比值明显低于正常对照组(33±8,2.5±0.6,P<0.01,t=3.299,2.768)。抑郁组的CD8(22±6)明显高于非抑郁组(15±7,P<0.01,t=15.215),抑郁组的CD4/CD8(1.3±0.4)明显低于非抑郁组(2.2±1.1,P<0.01,t=8.702)。抑郁组的CD8与SDS评分有明显的正相关(P<0.01,r=0.914),抑郁组的CD4/CD8与SDS评分有明显的负相关(P<0.05,r=-0.615)。结论:胃肠癌患者术后仍有明显抑郁反应。抑郁情绪反应可以影响癌症患者的细胞免疫。     

Synergistic and suppressive interactions among mouse T lymphocytes in the response to phytohemagglutinin

A synergistic effect in the proliferative response to phytohemagglutinin (PHA) can be observed in cultures containing a mixture of mouse CBA/Ca lymph node cells (LNC) and syngeneic CBA/T6T6 thymocytes (ThC) when compared to cultures containing only one cell type. This effect was analyzed, at various days of culture and in LNC- ThC mixtures of different ratios, by comparing the origin of the cells in mitosis (detected by caryotypic analysis), the stimulation of DNA synthesis, the number of blasts, and the percentage of blasts labeled after pulses of [3H]thymidine (detected by autoradiography). The following conclusions were reached: (a) ThC are induced to proliferate by the presence of LNC, while they are almost unresponsive to PHA when cultured alone; and (b) the strongest "synergistic" effect is exerted on LNC, whose proliferation is markedly enhanced. Evidence is presented that this last effect is not specific to the presence of ThC, but results from a dilution of LNC which retards the time when the culture reaches a critical concentration of blasts, above which proliferation progressively stops. Thus, conditions of culture allowing the response to PHA of a low concentration of LNC leads to the most prolonged T-cell proliferation. These observations may be relevant to the types of T- cell interactions, "synergistic" or "suppressive," occurring during in vitro or in vivo immune responses.     

黄芪对慢性肾功能衰竭患者免疫功能的影响

目的：探讨黄芪对慢性肾功能衰竭（ＣＲＦ）患者免疫功能的影响。方法：５１例ＣＲＦ患者随机分为２组，治疗组给予黄芪及西药治疗，对照组单用相同西药治疗。结果：５１例ＣＲＦ患者与健康人比较，单克隆抗体ＯＫＴ３、ＯＫＴ４及ＯＫＴ８均明显降低（Ｐ均＜０．０１）。治疗组治疗后ＯＫＴ８降低，ＯＫＴ４／ＯＫＴ８升高，与治疗前比较，Ｐ均＜０．０１，而对ＣＲＦ患者的体液免疫无影响。结论：黄芪具有调整ＣＲＦ患者细胞免疫的作用。     

Low serum bilirubin in chronic renal failure. Relation to haem metabolism.

In renal failure serum bilirubin values are lower than normal. When renal failure is moderate this decrease is not due to a reduced-red-cell mass or to low levels of serum albumin. In splenic fine-needle aspirates from patients with renal failure, conditions for haem degradation were normal as indicated by normal activities of haem oxygenase and biliverdin reductase. Nor were the in vitro activities of these enzymes significantly depressed in the presence of ultrafiltrates of uraemic sera or of high concentrations of creatinine, urea or methylguanidine. The capacity of plasma from patients with renal failure to bind bilirubin was less than that of normal plasma, which at least partially explains the observed low values of serum bilirubin. There remains the possibility that in renal failure some bilirubin is removed from the plasma by a hitherto unknown route.     

Progression to renal failure after nephrotoxic nephritis in rats studied by renal transplantation

We studied the relation between immunopathology and progressive renal failure after nephrotoxic nephritis (NTN) in rats. Thirty days after induction of nephritis by injection of rabbit anti-rat nephrotoxic serum, pairs of kidneys from 13 nephritic rats were transplanted into separate syngeneic recipients, one of whom had been pre-immunized with rabbit immunoglobulin G (IgG) whilst the other was naive. Progression to renal failure of the transplanted nephritic kidney was studied after removal of the recipient's own kidneys; results from right and left kidney from a single donor in pre-immunized and naive recipients were compared. There were substantial differences in autologous anti-rabbit IgG titres in naive and preimmunized recipients; despite this pairs of kidneys from the same donor had almost identical courses as assessed by proteinuria, serum creatinine and graft survival. There was substantial variation in survival of kidneys from different donors. But there were very strong correlations of graft survival with proteinuria (r = 0.97, t = 4.443, P less than 0.001) and reciprocal serum creatinine (r = 0.95, t = 4.32, P less than 0.001) in donors shortly before transplantation. We conclude that autologous antibody titres did not influence the progression to renal failure after nephrotoxic nephritis. The rate of progression was already determined at the time of transplantation.     

高龄慢性肾衰竭病人抑郁情绪的综合护理

[目的]了解高龄慢性肾衰竭(CRF)病人抑郁情绪发生情况,以便采取相应的护理对策。[方法]我院老年心肾科2000年—2005年60岁以上高龄CRF住院病人102例,入院采用抑郁量表(SDS)调查发现有85例存在不同程度的抑郁情绪,随机将其分为两组,对照组42人,行常规护理;干预组43人,行综合护理干预。护理干预3周后两组再次评分比较。[结果]护理3周后,干预组SDS评分明显低于对照组和本组干预前的SDS评分,其差异有统计学意义(P<0.05);临床症状缓解程度干预组好于对照组。[结论]高龄CRF病人抑郁情绪发生率高,必须予以高度重视,采取相应的综合护理干预可有效减轻病人的抑郁情绪,有助于病人的康复。     

Defective recognitive immunity in family aggregates of colon carcinoma.

Cancer-free individuals from family agregates of seemingly hereditary colon carcinoma were studied to determine the nature of their cell-mediated immune capacities in miexed leukocyte culture. Members of families who demonstrated no evidence of a precancerous condition such as polyposis coli did demonstrate substantial cellular immunopathology. Of these, 44% showed a decreased responsiveness of their peripheral mononuclear cells to allogeneic stimuli, and in a number of these individuals this deficiency clearly manifested itself as an inappropriate suppression of potentially normal lymphocyte blastogenic capacities by an adherent population of mononuclear leukocytes. This in vitro defect of recognitive immunity appears to be the same type of defect that has already been described for individuals with established maligancies. The pattern of phenotypic expression of this immunopathology within these families is not inconsistent with an hereditary disorder. Individuals from families with a known hereditary somatic precancerous condition usually did not demonstrate this immunopathology. It is appropriate to speculate that the defect of recognitive immunity in the former families could be contributory to the genesis of the colon carcinoma.     

Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen

Vaccinia infection interferes with the presentation of influenza Haemagglutinin (HA) and Nucleoprotein (NP) to class I-restricted CTL. The inhibitory effect is selective for certain epitopes, and is more profound during the late phase of infection. For influenza A/NT/60/68 NP, the block is present during both early and late phases of infection, and is selective for the COOH-terminal epitope defined by peptide 366-379, having no detectable effect on the presentation of the NH2-terminal epitope 50-63. The presentation of HA is inhibited only during the late phase of vaccinia infection. For both proteins, presentation is partially (NP) or completely (HA) restored by expression of rapidly degraded protein fragments in the vaccinia infected target cell. For HA, deletion of the NH2-terminal signal sequence completely overcomes the block. For NP, either a large NH2-terminal deletion or the construction of a rapidly degraded ubiquitin-NP fusion protein partially restores presentation. These results illustrate the relationship between degradation of viral proteins in the cytoplasm of an infected cell and recognition of epitopes at the cell surface by class I-restricted T cells.     

The mediator of cellular immunity. II. Migration of immunologically committed lymphocytes into inflammatory exudates

Peritoneal exudates from rats which have survived an infection with L. monocytogenes can protect cyclophosphamide-treated recipients against a Listeria challenge. They are more effective in this respect than cells obtained from the spleen or thoracic duct lymph. Since exudate cells from normal rats and inocula prepared from the resident peritoneal cell populations of infected donors are unable to inhibit the challenge infection, the protective cells must belong to a class of lymphocytes that emerges from the blood in response to inflammation. It is significant therefore that thoracic duct lymphocytes formed during an acute Listeria infection can move into exudates induced by a variety of inflammatory stimuli. The affinity of newly formed lymphocytes for inflamed tissue points to a mechanism whereby the host marshalls its cellular defenses at sites of bacterial invasion. The tendency of short-lived lymphocytes to leave inflamed vessels might also explain their short-circulating life-span.     

Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier Disease.

Tangier disease is a rare genetic disorder characterized by extremely low plasma levels of HDL and apo A-I, deposition of cholesteryl esters in tissues, and a high prevalence of cardiovascular disease. We examined the possibility that HDL apolipoprotein-mediated removal of cellular lipids may be defective in Tangier disease. With fibroblasts from normal subjects, purified apo A-I cleared cells of cholesteryl esters, depleted cellular free cholesterol pools available for esterification, and stimulated efflux of radiolabeled cholesterol, phosphatidylcholine, and sphingomyelin. With fibroblasts from two unrelated Tangier patients, however, apo A-I had little or no effect on any of these lipid transport processes. Intact HDL also was unable to clear cholesteryl esters from Tangier cells even though it promoted radiolabeled cholesterol efflux to levels 50-70% normal. Passive desorption of radiolabeled cholesterol or phospholipids into medium containing albumin or trypsinized HDL was normal for Tangier cells. Binding studies showed that the interaction of apo A-I with high-affinity binding sites on Tangier fibroblasts was abnormal. These results indicate that apo A-I has an impaired ability to remove cholesterol and phospholipid from Tangier fibroblasts, possibly because of a defective interaction of apo A-I with cell-surface binding sites. Failure of apo A-I to acquire cellular lipids may account for the rapid catabolism of nascent HDL particles and the low plasma HDL levels in Tangier disease.     

Cytokinetic analysis of the impaired proliferative response of peripheral lymphocytes from aged humans to phytohemagglutinin

The effect of donor age on the rate of cell entry into the proliferating pool and subsequent cell cycle duration for peripheral lymphocytes stimulated by phytohemagglutinin (PHA) were examined by using the bromodeoxyuridine incorporation-differential staining technique. Distribution curves for the appearance of metaphase cells in successive generations as a function of culture time were obtained and analyzed both graphically and by a computer simulation model. Peripheral lymphocytes from aged individuals (approximately 75 yr) were stimulated by PHA at approximately one-half of the rate of peripheral lymphocytes from young individuals (approximately 21 yr). Subsequent cell-cycle durations were estimated to range from 10.0 to 25.0 h for aged individual lymphocyte cultures and 10.6-15.6 h for young individual lymphocyte cultures. The possible significance of these findings to aging in general is discussed.